| 1. |
- Sjöholm, Hanna, 1975-
(author)
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Assessments and Risk Factors for Falls in Persons with Acute Stroke
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Background: Early identification of risk factors is crucial for reducing the high fall risk associated with stroke, and sex differences in relation to falls need to be further investigated. There is a lack of uniform, standardized, and reliable testing procedures for postural reactions, and existing tests assessing negotiating obstacles while walking cannot be performed when walking aids are used.Aim: To investigate the predictive validity of fall risk in persons with acute stroke for easily administered data and assessments, as well as to investigate the psychometric properties of two new tests.Methods: The Postural Rections Test (PRT) and the Cone Evasion Walk Test (CEW) were developed based on literature, and on input from an expert panel. To estimate the reliability of the PRT and CEW, video-recordings of 20 persons with acute stroke performing each item in the PRT and CEW were assessed by 10 physiotherapists on two occasions, at least two weeks apart. The construct validity of the CEW (n = 221), was examined in relation to selected corresponding tests, and predictive validity by correlating the CEW to falls within six months. In 124 women and 160 men the results from the PRT and CEW, along with other easily administered data and assessments on participant characteristics, functions, and activities were analyzed in relation to the number of days to the first fall by Cox regression, while fall incidence was analyzed by negative binomial regression, both for the total cohort, and for women and men separately. Sex differences in monthly fall incidence were analyzed with Poisson regression.Results: For the intra-rater reliability of the PRT, the overall proportion of agreement was 87 − 92% for the different postural reactions, and in median 9–10 out of 10 physiotherapists scored the same value for inter-rater reliability. In the CEW the intra-class correlation coefficients for intra-rater and inter-rater reliability were 0.88–0.98. The results showed expected poor to moderate correlations to the selected tests for construct validity, and to falls within six months. Participants touched significantly more cones on the side that was opposite to the side of their lesion. The Cox regression analysis showed that intake of more than eight medications, paresis in the arms, paresis in the legs, impaired protective reactions in sitting, and limitations in self-care activities were decisive risk factors for the time to the first fall, and according to the negative binomial regression, limitations in mobility activities was a decisive risk factor for high fall incidence in the total cohort (p<0.0005). The assessor’s judgment of a person’s six-month fall risk, was particularly well suited for identification of individuals with a high risk for multiple falls; however only in women when analyzed for each sex separately (p<0.0005). Compared to men, a higher number of fall risk factors were identified in women, including impaired mental functions, paresis in the arms, and limitations in several activities of self-care and mobility (p<0.0005). In men, the most decisive fall risk factors were intake of a high number of medications, intake of antidepressants, and mobility limitations (p=0.001). Fall incidence during the first month from discharge was significantly higher in men compared to women.Conclusions: The PRT and CEW can be reliably used in persons with acute stroke, and are valid for assessment of fall risk. A high quantity and wide range of rapid and easily collected data can be used for identification of persons at high risk for falls. The risk factors differed in part when analyzing the time to the first fall, and six-month fall incidence, and different fall risk factors were the most decisive when analyzed separately in women and men. Monthly fall incidence was higher in men during the first month.
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| 2. |
- Skogh, Elisabeth, 1952-
(author)
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Studies on Variability in Olanzapine Disposition
- 2011
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Licentiate thesis (other academic/artistic)abstract
- Schizophrenia and schizoaffective disorders are chronic conditions with a significant impact on many functions. Positive, negative, cognitive and motor symptoms appear in different degrees and constellations. Antipsychotics are of fundamental importance to reduce symptoms. However, insufficient clinical effect and adverse drug reactions (ADRs) are important limitations of this drug therapy. Olanzapine (OLA) is a second-generation antipsychotic (SGA) drug widely used in the treatment of schizophrenia and schizoaffective disorder. The drug has well-documented effects against positive symptoms and has been claimed to be efficacious also against negative symptoms.This thesis comprises of two studies. The aim of study 1 was to investigate factors that may influence the inter- and intra-individual variability of steady-state trough concentrations of OLA and its N-desmethyl metabolite (DMO) in serum. This was done in a cohort of patients treated with oral OLA in a routine clinical setting. In study 2 steady-state trough serum OLA and DMO concentrations were studied in relation to cerebrospinal fluid (CSF) OLA and DMO concentrations in patients with schizophrenia or schizoaffective disorder, medicated with oral OLA as the only antipsychotic drug. We also analysed the effects of age, gender smoking and concomitant medication in both studies and in study 2 we also analysed polymorphisms in genes with suggested importance for OLA disposition. The drug metabolizing enzymes CYP1A2 and CYP2D6 have earlier been found to be of importance for OLA metabolism and one animal study has suggested a role for P-gp for the transport of OLA into the brain. Therefore we analysed the influence of single nucleotide polymorphisms in the CYP1A2 gene (-3860G>A, -2467T>delT, -739T>G, -729C>T, -163C>A, and in the CYP2D6 gene (*3, *4, *5,*6, and*41) and in the ABCB1 gene (1236C>T, 3435C>T, and 2677G>A/T).Study 1 started as a post-marketing surveillance project. In 1997 a high-performance liquid chromatography (HPLC)-based therapeutic drug monitoring (TDM) routine for serum OLA and DMO was established. During 1997–1999, a total of 753 TDM requests for a total of 545 Swedish patients were analysed. Additional patient information on certain clinical variables was collected on a specifically designed TDM request form. Samples from 194 patients were found to be eligible for further scrutiny. We found that the concentration-to-dose ratio (C/D) for OLA varied 25-fold and that of DMO 22-fold between individuals. The intraindividual variability over time was lower. Women had significantly higher median C/D ratio for OLA than men. However, the higher C/D ratio for OLA in women was statistically significant only in the non-smoking group. Non-smokers had significantly higher C/D ratio for OLA than smokers. Smokers received significantly higher daily doses of OLA than non-smokers. In the group with reported ADRs, the serum OLA concentration was 22% higher than in the group without ADRs. Patients co-medicated with carbamazepine had a 71% lower C/D ratio for OLA than patients who did not co-medicate with carbamazepine.Study 2 included 37 Caucasian outpatients (10 smokers and 27 non-smokers). CSF was collected from 29 out of them. Because of very low OLA and DMO concentrations in CSF, a new liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for determination of OLA and DMO in serum and CSF was developed. We found a strong correlation between serum and CSF concentrations of OLA and a somewhat weaker corresponding correlation regarding DMO. The median CSF concentrations of OLA and DMO were on an average 13% and 16% of the serum levels. Non-smokers had higher (P <0.01) C/D ratio for OLA in serum and in CSF than smokers. Extensive metabolizers (EM) of CYP2D6 had higher daily OLA dosages than poor metabolizers (PM) when the influence of smoking was taken into account. EM smokers also showed lower CSF C/D for DMO than PM smokers. The DMO/OLA ratio in CSF showed a similar pattern, with a statistically significant combined effect of smoking and CYP2D6 genotype, EM smokers having the lowest and PM smokers the highest ratio. The combination of smoking and CYP2D6 genotype also affected the CSF/serum DMO ratio, PM smokers having the highest and EM smokers the lowest ratio (mean 20%, vs 9.5%). Patients co-medicating with benzodiazepines also showed higher CSF DMO/OLA ratio than patients without benzodiazepines. Moreover, DMO concentrations in CSF in relation to serum were higher in benzodiazepine users than in patients not comedicating with benzodiazepines (mean 24% vs 14.4%). Smoking habits did not affect these results. Carriers of the ABCB1 1236T/2677T/3435T haplotype had higher serum and CSF OLA concentrations than patients without this haplotype. The C/D ratios for serum DMO decreased with increasing age (P < 0.05).In summary, smoking habits and co-medication with carbamazepine should be taken into consideration when dosing OLA. In study 1 we noted that women had higher serum C/D OLA ratio than men among non-smokers. This could not be confirmed in study 2, probably due to the small study population. Polymorphisms in genes of importance for OLA metabolism (CYP1A2 and CYP2D6) and transport (ABCB1) over membranes have some, but probably a minor, effect on serum and CSF concentrations. Larger studies are needed to confirm these observations. Smoking in combination with CYP2D6 polymorphism and the use of benzodiazepines affected the DMO metabolism in the brain in this study. However, because of low precision in the method at low DMO concentrations and a low number of patients, these results must also be confirmed in larger studies. The strong correlation between serum and CSF OLA concentrations established in study 2 indicates that factors influencing serum concentrations (such as smoking) also influence these concentrations in CSF. When patients are non-responsive to treatment, not compliant, vulnerable to ADRs on standard doses, or when drug interactions are suspected, TDM serum-OLA concentrations can be used as a diagnostic tool. Therapeutic drug monitoring is also of value to optimize long-term treatment of patients as environmental factors such as smoking and drug interactions may differ over time and could markedly interact with a patient´s metabolic capacity and thereby the therapeutic outcome.
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| 3. |
- Tjäderborn, Micaela, 1983-
(author)
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Psychoactive prescription drug use disorders, misuse and abuse : Pharmacoepidemiological aspects
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Background: There is a widespread and increasing use of psychoactive prescription drugs, such as opioid analgesics, anxiolytics, hypnotics and anti-epileptics, but their use is associated with a risk of drug use disorder, misuse and abuse. Today, these are globally recognized and emerging public health concerns.Aim: The aim of this thesis is to estimate the prevalence of psychoactive prescription drug (PPD) use disorders, misuse and abuse, and to investigate the association with some potential risk factors.Methods: A study using register data from forensic cause of death investigations investigated and described cases of fatal unintentional intoxication with tramadol (Study I). Based on register data on spontaneously reported adverse drug reactions (ADRs) reported cases of tramadol dependence were investigated and summarised (Study II). In a study in suspected drug-impaired drivers with a toxicology analysis confirming the intake of one out of five pre-specified PPDs, the prevalence of non-prescribed use was assessed and associated factors were investigated (Study III). From a cohort of patients initiating prescribed treatment with pregabalin, using data on prescription fills, a study investigated longitudinal utilisation patterns during five years with regards to use of the drug above the maximum approved daily dose (MAD), and factors associated with the utilisation patterns (Study IV).Results: In the first study, 17 cases of unintentional intoxications were identified, of which more concerned men, the median age was 44 years and the majority used multiple psychoactive substances (alcohol, illicit drugs and prescription drugs). The second study identified 104 spontaneously reported cases of tramadol dependence, in which more concerned women, the median age was 45 years, and a third reported a history of substance abuse and 40% of past psychoactive medication use. In the third study, more than half of the individuals suspected of drug-impaired driving used the drug without a recent prescription. Non prescribed use was most frequent in users of benzodiazepines and tramadol, and was more likely in younger individuals and in multiple-substance users. In the last paper five longitudinal utilisation patterns were found in pregabalin users, with two patterns associated with a particularly high risk of doses above the maximum approved dosing recommendation. This pattern of use was associated with male sex, younger age, non-urban residency and a recent prescribed treatment with an antiepileptic or opioid analgesic drug.Conclusions: This thesis shows that psychoactive prescription drug use disorders, misuse and abuse occur and may have serious and even fatal consequences. The prevalence varies between different drugs and populations. Abuse and misuse seem to be more common in young people. Fatal intoxications and misuse of prescribed drugs may be more common in men, while drug use disorders following prescribed treatment may be more common in women and non-prescribed use equally distributed between women and men. Individuals with a history of mental illness, substance use disorder or abuse, or of past use of psychoactive medications are likely important risk groups. In summary, the findings suggest a potential for improvements in the utilisation of psychoactive prescription drugs. The results may be useful in the planning of clinical and regulatory preventive interventions to promote the rational, individualised and safe use of such drugs.
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| 4. |
- Hedna, Khedidja, 1978-
(author)
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Inappropriate prescribing, non-adherence to long-term medications and related morbidities : Pharmacoepidemiological aspects
- 2015
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Doctoral thesis (other academic/artistic)abstract
- Background: Inappropriate use of medications (IUM), in particular inappropriate prescribing and non-adherence to prescribed medications, are important causes of drug-related morbidities (DRMs). They are increasing problems with the ageing populations and the growing burden of chronic conditions. However, research is needed on the association of IUMs with DRMs in outpatient settings and in the general population.Aim: The aim of this thesis is to estimate and analyse the burden of potentially inappropriate prescriptions (PIPs) in the elderly and non-adherence to long-term medications among adults across care settings, and to investigate how IUM is associated to DRMs.Methods: A meta-analysis summarised the previous evidence on the percentage of adverse drug reactions (ADRs) associated to IUM across healthcare settings (Study I). From a cohort in the general population, using medical records and register data, the prevalence of PIPs in the elderly and its association with ADRs were estimated retrospectively (Study II). From the same cohort, the factors associated with refill non-adherence to antihypertensive therapy, considering the use of multiple medications, and the association between non-adherence and sub-therapeutic effects (STEs) were investigated (Study III). A survey assessed the refill behaviour to antihypertensive, lipid lowering and oral antidiabetic medications (undersupply, adequate supply and oversupply), and its association with perceived ADRs and STEs (Study IV).Results: IUM was the cause 52% and 45% of ADRs occurring in adult outpatients and inpatients respectively. Across healthcare settings, 46% of the elderly refilled PIPs over a 6-month period; PIPs were considered the cause of 30% of all ADRs; and the elderly who were prescribed PIPs had increased odds to experience ADRs (OR 2.47, 95% CI 1.65-3.69). In total, 35% was nonadherent to the full multidrug therapy and 13% was non-adherent to any medication (complete non-adherence). Sociodemographic factors (working age and lower income) were associated with non-adherence to any medication, while clinical factors (use of specialised care, use of multiple medications, and being a new user) with non-adherence to the full multidrug therapy. STEs were associated with non-adherence to any medication a month prior to a healthcare visit (OR 3.27, 95% CI 1.27-8.49), but not with long-term measures of non-adherence. Among survey respondents, 22% of the medications were oversupplied and 12% were undersupplied. Inadequate refill behaviour was not associated with reporting ADRs or STEs (p<0.05).Conclusions: A large proportion of ADRs occurring in hospital is caused by IUM, but more knowledge is needed in other settings. PIPs are common in the elderly general population and associated with ADRs. Therefore decreasing PIPs could contribute towards ADR prevention. Considering the use of multiple medications may help to better understand the factors associated with non-adherence to a multidrug therapy for tailoring the interventions to patient needs. Monitoring the adherence prior to a healthcare visit may facilitate interpreting STEs. Yet, the absence of an association between long-term measures of refill non-adherence with clinical and perceived DRMs suggest the need to enhance the knowledge of this association in clinical practice. In summary, this thesis shows a significant potential for improvements of medication use and outcomes.
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| 5. |
- Skoglund, Karin, 1982-
(author)
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Influence of CYP3A enzymes and ABC transporters on the activity of tyrosine kinase inhibitors in chronic myeloid leukemia
- 2013
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Doctoral thesis (other academic/artistic)abstract
- The introduction of imatinib, a tyrosine kinase inhibitor (TKI), in the treatment of chronic myeloid leukemia (CML) was a major break-through and the first drug that was successfully designed to target the specific mechanism of a malignant disease. Imatinib still remains as the standard treatment of newly diagnosed CML patients although a second generation of TKIs has also been approved for first-line CML treatment.Most patients achieve a good therapeutic effect with imatinib, but some patients are resistant to the drug and are at greater risk of disease progression. In order to further improve CML treatment, a better understanding of the underlying reasons for variable responses to imatinib and the second generation TKIs is important.A number of potential determinants of imatinib response have been suggested, including interindividual variability in pharmacokinetics. Variations in drug metabolism and cellular transport might contribute to the large variations observed in imatinib plasma concentrations and might, therefore, affect the amount of drug that reaches target CML cells. Imatinib is primarily metabolized by the CYP3A hepatic enzymes that are known to be highly variable in activity between different individuals. Imatinib is also a substrate of the ABCB1 and ABCG2 efflux pumps that potentially regulate the elimination of imatinib from the plasma. The ABCB1 and ABCG2 genes are polymorphic and contain single nucleotide polymorphisms (SNPs) that might influence the transport capacity of these proteins. The primary aim of the present thesis was to investigate the influence of CYP3A metabolic activity and cellular transport mediated by genetic variants of ABCB1 and ABCG2 on the response to imatinib and the second generation TKIs used for CML therapy.In vivo CYP3A activity and plasma concentrations of imatinib and its pharmacologically active metabolite CGP74588 were analyzed in CML patients treated with imatinib. CYP3A phenotypes were correlated to plasma concentrations and imatinib outcome 12 months after initiation of treatment. The influence of ABC transport on TKI efficacy was evaluated in vitro by the transduction of genetic variants of ABCB1 and ABCG2 into the CML cell line K562. Functionality of the transport proteins was evaluated by measuring protein expression levels on the cell surface, the intracellular accumulation of TKIs, and the ability of ABCB1 and ABCG2 variants to protect cells from TKI cytotoxicity.We found that CYP3A metabolic activity does not influence the drug plasma concentrations or the therapeutic outcome of imatinib in CML patients. These findings indicate that even though imatinib is primarily metabolized by CYP3A this metabolic activity is not the rate-limiting step in imatinib elimination. CYP3A activity, therefore, is not a suitable predictive marker of imatinib outcome. The in vitro studies revealed that the ABCB1 variants investigated here do not alter the transport of imatinib, CGP74588, dasatinib, or nilotinib. In contrast, the ABCG2 SNPs 421C>A, 623T>C, 886G>C, and 1574T>G significantly impaired the cellular efflux of imatinib, CGP74588, dasatinib, and nilotinib and could possibly influence transport of these TKIs in vivo. It was also found that CGP74588 is by far a better substrate than imatinib for both ABCB1 and ABCG2, and this might have implications in patients with high levels of CYP3A activity. In conclusion, our studies show that ABCG2 SNPs might be important for prediction of imatinib outcome in vivo. On the other hand, CYP3A activity and the ABCB1 SNPs investigated in this study are not likely to be useful as predictors of imatinib outcome.
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| 6. |
- Strandell, Johanna, 1979-
(author)
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Drug interaction surveillance using individual case safety reports
- 2011
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Doctoral thesis (other academic/artistic)abstract
- Background: Drug interactions resulting in adverse drug reactions (ADRs) represent a major health problem both for individuals and society in general. Post-marketing pharmacovigilance reporting databases with compiled individual case safety reports (ICSRs) have been shown to be particularly useful in the detection of novel drug - ADR combinations, though these reports have not been fully used to detect adverse drug interactions.Aim: To explore the potential to identify drug interactions using ICSRs and to develop a method to facilitate the detection of adverse drug interaction signals in the WHO Global ICSR Database, VigiBase.Methods: All six studies included in this thesis are based on ICSRs available in VigiBase. Two studies aimed to characterise drug interactions reported in VigiBase. In the first study we examined if contraindicated drug combinations (given in a reference source of drug interactions) were reported on the individual reports in the database, and in the second study we examined the scientific literature for interaction mechanisms for drug combinations most frequently co-reported as interacting in VigiBase. Two studies were case series analyses where the individual reports were manually reviewed. The two remaining studies aimed to develop a method to facilitate detection of novel adverse drug interactions in VigiBase. One examined what information (referred to as indicators) was reported on ICSRs in VigiBase before the interactions became listed in the literature. In the second methodological study, logistic regression was used to set the relative weights of the indicators to form triage algorithms. Three algorithms (one completely data driven, one semi-automated and one based on clinical knowledge) based on pharmacological and reported clinical information and the relative reporting rate of an ADR with a drug combination were developed. The algorithms were then evaluated against a set of 100 randomly selected case series with potential adverse drug interactions. The algorithm’s performances were then evaluated among DDAs with high coefficients.Results: Drug interactions classified as contraindicated are reported on the individual reports in VigiBase, although they are not necessarily recognised as interactions when reported. The majority (113/123) of drug combinations suspected for being responsible for an ADR were established drug interactions in the literature. Of the 113 drug interactions 46 (41%) were identified as purely pharmacodynamic; 28 (25%) as pharmacokinetic; 18 (16%) were a mix of both types and for 21 (19%) the mechanism have not yet been identified. Suspicions of a drug interaction explicitly noted by the reporter are much more common for known adverse drug interactions than for drugs not known to interact. The clinical evaluation of the triage algorithms showed that 20 were already known in the literature, 30 were classified as signals and 50 as not signals. The performance of the semi-automated and the clinical algorithm were comparable. In the end the clinical algorithm was chosen. At a relevant level, 38% were of the adverse drug interactions were already known in the literature and of the remaining 80% were classified as signals for this algorithm.Conclusions: This thesis demonstrated that drug interactions can be identified in large post-marketing pharmacovigilance reporting databases. As both pharmacokinetic and pharmacodynamic interactions were reported on ICSRs the surveillance system should aim to detect both. The proposed triage algorithm had a high performance in comparison to the disproportionality measure alone.
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| 7. |
- Jönsson, Anna K., 1976-
(author)
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Drug-related morbidity and mortality : Pharmacoepidemiological aspects
- 2007
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Doctoral thesis (other academic/artistic)abstract
- Adverse drug reactions (ADRs) constitute a significant health problem with consequences for the patient as well as for society. Suspected ADRs have been reported to occur in about 2-14% of hospitalised patients. In about 5% of deceased hospitalised patients suspected ADRs may have caused or contributed to the fatal outcome. When a pharmaceutical drug is approved for marketing, the drug has been tested only on a limited number of patients (often <6000) for a limited time period in a controlled environment. Hence mostly common ADRs are detected in these trials. Moreover, certain patient groups, for example patients with co-morbidities, elderly patients, children and pregnant women are often not included in these studies. Thus, it is important to closely monitor the use of drugs after marketing to observe new effects and detect new ADRs.The aim of this thesis is to describe the pattern of pharmaceutical substance use related to morbidity and mortality and to investigate two serious ADRs. We have studied the incidence of fatal ADRs, fatal intoxications, cerebral haemorrhage related to warfarin treatment and venous thromboembolism (VTE) related to treatment with antipsychotic drugs.Observational studies form the basis for this thesis. Data from the Swedish Cause of Death Register, medical case records, the Swedish database on ADRs, the forensic pathology and forensic toxicology databases, and Swedish and Danish hospital discharge registers, Danish prescription registers, and civil registry systems were used.In Paper I we found that 3% of all fatalities in a Swedish population were related to a suspected ADR. Of the deceased hospitalised patients, 6% were related to a suspected ADR. Haemorrhage was the most commonly observed fatal suspected ADR, accounting for almost two-thirds of the events and anticoagulantia was the most common drug group associated with fatal suspected ADRs (almost 50%). A suspected intoxication could have contributed to the fatal outcome in 0.6% of the deceased. Among the fatal intoxications in Swedish medico-legal autopsies studied in Paper II, on average four substances were detected per case. The five most commonly detected substances in individuals with a fatal intoxication were ethanol, propoxyphene, paracetamol, diazepam and flunitrazepam. Among patients diagnosed with cerebral haemorrhage, 10% (59 cases) were treated with warfarin at onset of symptoms (Paper III). Of these, 7 cases (12%) were considered to have been possibly avoidable since the patients were treated with concomitant drugs that have the potential to enhance warfarin effects. The results from Paper IV and Paper V in combination with the published literature suggest that patients treated with antipsychotic drugs have an increased risk for VTE. Compared with non-users, an adjusted odds ratio for VTE of 2.0 was found for users of any antipsychotic drugs in a Danish population. In a medico-legal autopsy series, an adjusted odds ratio for fatal pulmonary embolism of 2.4 and 6.9 was found for users of first-generation low-potency antipsychotics and second-generation antipsychotics, respectively.In summary, drug-related morbidity and mortality is a significant problem and suspected ADRs contribute to a substantial number of deaths. Fatal intoxications are relatively common and it is important to observe changes in patterns of substances associated with fatal intoxications to be able to discover new trends and monitor effects of preventive work. A significant proportion of warfarin-related cerebral haemorrhage was caused by drug-drug interactions and was considered possible to avoid. Users of antipsychotic drugs may increase the risk of VTE.
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| 8. |
- Kindstedt, Jonas, 1986-
(author)
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Medication-related problems and psychotropic drug use in vulnerable older populations : a focus on acute hospital admissions and cognitive impairment
- 2023
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Doctoral thesis (other academic/artistic)abstract
- The ageing process involves several physiological changes that affect both pharmacodynamics and pharmacokinetics and that, in combination with a heavier disease burden and more extensive use of medicines, put older people at higher risk of medication-related problems and associated clinical outcomes. The older population is often treated as a homogenous group, when in fact there are factors that render certain individuals more vulnerable to adverse drug effects and other types of medication-related problems. Older people encountered in the acute medical care setting and/or individuals with varying degrees of cognitive impairment are especially vulnerable in that context. The overall aim of this thesis was to describe and understand medication use in certain vulnerable subgroups of older people, which in turn might identify suitable target populations in which medication-related problems can be prevented or managed through interventions or similar efforts.Paper I presented, in the form of a study protocol, a clinical pharmacist intervention intended to reduce the risk of medication-related readmission to hospital among people aged 75 years or older during transitions of care. Based on 300 participants from the intervention study, approximately 50% had been readmitted to hospital within 180 days of being discharged from the hospital. Both heart failure and cognitive impairment, the latter identified through a four-item test, were predictors of early readmission. Altogether, the study population seems relevant for the purpose of the intervention; whether the intervention model is effective remains to be determined.Based on the same sample of study participants, paper II found that approximately one third of the 300 index hospital admissions were possibly medication related. Moreover, possibly medication-related hospital admissions were negatively associated with the fewest positive/correct answers on the four-item screening tool for cognitive impairment, which suggests that those clinical events might be less prevalent among people with cognitive impairment when exploring the association cross-sectionally. Both papers III and IV were registry-based studies, and their overall objective can be summarized as to describe psychotropic drug use and associated factors among older people with major neurocognitive disorder (NCD). Paper III focused on differences between major NCD subtypes, whereas paper IV compared people with major NCD against matched references from the total older population. In brief, overall psychotropic drug use was notably higher among people with major NCD, although generally in line with national treatment guidelines in terms of individual drugs of choice. The use of hypnotic drugs was also extensive in the reference group, and deprescribing efforts seem warranted, although longitudinal studies that focus on long-term use could provide a better picture of the potential problem. Nursing home stay was also positively associated with psychotropic drug use for all classes of psychotropic drugs, and the difference was most prominent for antipsychotic drugs. In that context, over 1,200 people in the reference population, most of them nursing home residents, had filled prescriptions for antipsychotic drugs, a figure indicating that the management of neuropsychiatric symptoms might also be an issue among older people who, due to various circumstances, have not been examined and diagnosed with neurocognitive disorders. Regarding major NCD subtypes, individuals with Lewy body dementia had, except for antidementia drugs, higher odds of psychotropic drug use than did those with Alzheimer’s disease. For example, the odds of antipsychotic drug use were more than twice as high, which is a worrying figure given that people with Lewy body dementia are extremely sensitive to the adverse effects of those specific drugs.In conclusion, this thesis illustrates the heterogeneity of demographics and drug use among older people and indicates that certain types of medication-related problems may be more relevant in certain older subpopulations. Medicines appear to be involved in many hospital admissions of older people, and the acute medical setting and subsequent care transitions are likely an important focus of pharmaceutical interventions. However, psychotropic drugs are probably not a major issue in that specific context. Efforts to reduce psychotropic drug use are likely more relevant to people with major NCD, especially in the nursing home setting. Antipsychotic drug exposure among persons with Lewy body dementia could be one such focus, especially since there are other better-balanced pharmacological treatment options for these individuals in terms of efficacy and safety profile.
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